Abstract
Recently, we have shown that oligo-arginine peptide (i.e., R11), a unique cell-permeable peptide (CPP), can be used as an imaging probe for prostate cancer detection. In this study, the mechanism(s) of oligo-arginine peptide in prostate cells was further analyzed. The length of the oligo-arginine peptide appears to be critical for the efficiency of uptake by prostate cells: poly (11)-arginine (R11) > poly (9)-arginine (R9) > poly (13)-arginine peptide (R13). The uptake of R11 peptide by prostate cells is mediated by macropinocytosis as evidenced by the fact that uptake can be blocked by a macropinocytosis inhibitor. However, the use of an inhibitor for carbohydrate chain elongation of glycosaminoglycan or inhibitors for carbohydrate synthesis of glycoprotein via either O-link or N-link showed minimal effects on R11 uptake. Nevertheless, pentosan sulfate (PentS) or dextran sulfate (DS) exhibited the highest inhibitory effect on R11 uptake in several prostate cells treated with various soluble glycosaminoglycans (GAGs) or anionic polymers. It is known that laminin receptor has been characterized as a PentS binding partner. Knocking down 37LRP (laminin receptor precursor) expression in prostate cells showed a reduction in their ability to uptake R11 peptides. In conclusion, laminin receptor is one of the initial binding site(s) responsible for R11 peptide uptake in prostate cells.
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Acknowledgments
We thank Ms. Crystal Gore for the editorial assistance. This work was partially supported by the Prostate Cancer Research Program of the United States Army Medical Research and Materiel Command (W81XWH-08-1-0305 and W81XWH-04-1-0222) and a Clinical Innovator Award from the Flight Attendant Medical Research Institute. The authors declare that they have no conflict of interest.
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Zhou, J., Liu, W., Pong, RC. et al. Analysis of oligo-arginine cell-permeable peptides uptake by prostate cells. Amino Acids 42, 1253–1260 (2012). https://doi.org/10.1007/s00726-010-0817-7
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DOI: https://doi.org/10.1007/s00726-010-0817-7